The present invention is concerned with a novel process for the manufacture of 5-cyano-4-lower alkyl-oxazoles. These oxazoles form an important group of substances. For example, 5-cyano-4-methyl-oxazole is a valuable intermediate in the synthesis of pyridoxine (vitamin B.sub.6).
Several processes for the manufacture of 5-cyano-4-methyl-oxazole by the dehydration of 5-carbamoyl-4-methyl-oxazole have already been described. Thus, this dehydration has been carried out, for example, in the presence of phosphorus pentoxide see Helv. Chim. Acta 43, 1522-1530 (1960)!. The disadvantages of this process are, however, the low yield of product, which is presumably due to the carbonization which occurs very readily in this reaction, and the formation of phosphate byproduct which is considered to be a problematic waste product.
An improvement in this process is achieved by reacting 5-carbamoyl-4-methyl-oxazole with phosphorus pentoxide in the presence of quinoline as the solvent U.S. Patent (U.S. Pat. No.) 3,222,374!. However, this process also has disadvantages which result from the toxicity of the quinoline, its unpleasant smell as well as its thermal instability. Moreover, quinoline is a relatively expensive solvent. The regeneration of the quinoline, the required use of stoichiometric amounts of phosphorus pentoxide, the costly working-up of the byproducts of the phosphorus pentoxide (phosphates) as well as their disposal in an environmentally proper manner represent further problems.
Another known process for the manufacture of 5-cyano-4-methyl-oxazole comprises reacting 5-carbamoyl-4-methyl-oxazole with a lower alkanecarboxylic acid anhydride and subjecting the reaction mixture or the 4-methyl-5-(N-lower alkanoylcarbamoyl)-oxazole isolated therefrom to a pyrolysis European Patent Publication (EP) 10 697!. However, the final pyrolytic step has certain disadvantages, especially corrosion problems which occur with the reactor materials and the formation of byproducts which are difficult to recycle. Further, the high temperature at which the pyrolysis must be effected is a disadvantage.
The process described in U.S. Pat. No. 4,026,901 comprises catalytically dehydrating 5-carbamoyl-4-methyl-oxazole while heating at a high temperature in the presence of phosphorus pentoxide on a solid carrier. Disadvantages in this process are the handling of 5-carbamoyl-4-methyl-oxazole, especially the sublimation which is of prime consideration and simultaneously the solid dosing of the low volatile starting material, as well as, moreover, the formation and the disposal in an environmentally proper manner of the phosphate byproduct.
Further, the one-step conversion of ethyl 4-methyl-oxazole-5-carboxylate into 5-cyano-4-methyl-oxazole is described in U.S. Pat. No. 4,772,718. In this process the corresponding oxazole ester is converted into 5-cyano-4-methyl-oxazole in the presence of ammonia and a zirconium oxide or hafnium oxide catalyst in the gas phase. Disadvantages here are, however, the use of a relatively expensive catalyst as well as--in order to achieve an optimum reaction control--the maintenance of very precise reaction conditions, inter alia an inconveniently high reaction temperature. The industrial cost is accordingly high.
The gas phase dehydration of 5-carbamoyl-4-methyl-oxazole to 5-cyano-4-methyloxazole described in EP 492 233 has the disadvantage that the conversion must be carried out at reaction temperatures of about 400.degree. C. to about 500.degree. C. and at a high pressure, viz. of about 50 to about 300 kPa. Moreover, a high industrial cost is involved.
A further process is disclosed in U.S. Pat. No. 5,502,212 where 5-carbamoyl-4-lower alkyloxazoles are dehydrated to the corresponding 5-cyano-4-lower alkyl-oxazoles by reaction of the starting material with an N,N-disubstituted formamide and cyanuric chloride in a polar, aprotic organic solvent.
A process for the preparation of nitriles from carboxamides at a low temperature is described in Tetrahedron Letters 19, 1501-1502 (1971). The dehydration is effected by reaction with a two-fold molar excess of titanium tetrachloride. No reference is made to the dehydration of oxazolecarboxamides or compounds of similar structure.